NCT07103681

White Matter Distortion and Dementia Biomarkers in Normal Pressure Hydrocephalus (NPH)

Observational Study to Investigate the Effect of White Matter Tract Distortion and Neurodegenerative Biomarkers on Shunt-responsiveness in Idiopathic Normal Pressure Hydrocephalus (iNPH)

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Accepted

Summary

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a progressive condition of the elderly that results in severe disability. iNPH can dramatically respond to Cerebral spinal fluid(CSF)-shunting where excess ventricular fluid is diverted from the brain. Not all patients with iNPH respond to CSF-shunting however. The reasons for this are uncertain. Aim 1: To understand if specific nerve pathways (white matter tracts) that are near ventricles are damaged in patients that respond to shunting as opposed to those that do not. Aim 2: Can we explain shunt non-responsiveness by screening for dementia like illnesses (neurodegeneration) using a large array of methods. Aim 3: To understand whether wearable activity and bed sleep monitors are palatable in a NPH population and to understand if these metrics relate to quality of life. Aim 4: To see whether self-administered digital cognitive assessments can measure improvements pre and post surgery.

Detailed description

This single-centre observational cohort study will follow 50 patients diagnosed with symptomatic Normal Pressure Hydrocephalus (NPH) (idiopathic or late presenting congenital hydrocephalus and not secondary hydrocephalus) through their clinical journey, from initial assessment to post-CSF shunt surgery or a time when surgery is decided against. Separate groups of 50 asymptomatic individuals with chronic hydrocephalus and non-hydrocephalus individuals will act as controls. Participants will undergo comprehensive clinical assessments including gait, cognitive and urinary evaluations, quality of life measures, serum and CSF degenerative biomarker analysis, diffusion-weighted Magnetic Resonance Imaging (MRI) and optional brain and skin biopsies. Data collection will focus on capturing changes in clinical presentation and imaging findings before and after shunting. REDCap will be utilised as the primary tool for data storage. Primary outcome measures assess pre and post-shunting imaging changes in shunt-responders and non-responders. Shunt response will be defined as 10% improvement in gait speed. Secondary outcomes evaluate the relationship between biomarkers and clinical outcomes. Longitudinal data will help identify factors distinguishing responders from non-responders, with descriptive and inferential statistics used.

Conditions

• Normal Pressure Hydrocephalus

Interventions

Type	Name	Description
PROCEDURE	Ventriculoperitoneal Shunt (VP)	VP Shunt surgery involves surgical insertion of a catheter (tube) to divert brain fluid from the cerebral ventricles to the abdominal peritoneum. This will be performed in Group 1 patients as clinically indicated.
PROCEDURE	Brain and Skin Biopsy	Brain and skin biopsy's may be taken during the VP shunt to assist in histological analysis for neurodegenerative changes.
DIAGNOSTIC_TEST	MRI Brain	MRI brain with diffusion imagining will be performed before and after shunt surgery.

Timeline

• Start date: 2025-03-25
• Primary completion: 2028-02-01
• Completion: 2029-02-01
• First posted: 2025-08-05
• Last updated: 2026-03-27

Locations

1 site across 1 country: United Kingdom